Evaluation of effects of curcumin on acute esophagitis in the corrosive esophagitis model in rats.

Ingestion of a corrosive substance may cause corrosive esophagitis. Curcumin has anti-inflammatory and mucosal protective effects. In this study, the effects of curcumin on the acute phase of corrosive esophagitis were investigated. Twenty-seven Wistar Albino rats were divided into four groups; sham (group I), control (group II), and experiment groups (group III, 100 mg/kg curcumin; group IV, 200 mg/kg curcumin). Forty percent sodium hydroxide solution was used to erode the esophagi of rats in groups other than the sham group. Curcumin was applied to animals in the experiment groups 10 min after the corrosion. After 24 h, animals were sacrificed, and esophagus samples were collected. According to the histopathological examination, the muscularis mucosa damage was regressed from 100% in group II to 71.4% in group III and 50% in group IV. Mild level of damage and collagen deposition in the tunica muscularis regressed from 66.7% of the animals in the control group to 42.9% in group III and to none in group IV. Further, an increase in submucosal collagen was present in all samples from groups II and III, while 83.3% of samples had an increase in submucosal collagen in group IV. There was a significant difference in the histopathological total score between the control group and group IV (p=0.02). The results showed that the administration of curcumin in a dose-dependent manner can relieve the acute phase of corrosive esophagitis.

Comparative Assessment of Outcomes in Drug Treatment for Smoking Cessation and Role of Genetic Polymorphisms of Human Nicotinic Acetylcholine Receptor Subunits.

Objective: To investigate the effects of genetic polymorphisms of human nicotinic acetylcholine receptor subunits α3, α4 and α5, which are encoded by CHRNA3, CHRNA4 CHRNA5 genes, respectively, on nicotine addiction and outcomes of pharmacological treatments for smoking cessation. Methods: A total of 143 smokers and 130 non-smokers were included. Genotyping for CHRNA3 rs578776, CHRNA4 rs1044396-rs1044397, CNRNA5 rs16969968 polymorphisms was performed by PCR, flowed by RFLP. Clinical outcomes and success rates of pharmacological treatments for smoking cessation with nicotine replacement therapy (NRT), bupropion or varenicline were determined at the 12th week of the treatment. Results: Overall, 52 out of 143 (36.4%) smokers who received pharmacotherapy were able to quit smoking. Success rates for smoking cessation were similar for female (30.3%) and male (41.6%) subjects (p = 0.16). The success rate for smoking cessation treatment with varenicline (58.5%) was significantly higher as compared to other treatments with NRT (20.0%), bupropion (32.3%) or bupropion + NRT (40.0%) (chi-square test, p = 0.001). Smoker vs. non-smoker status and the clinical outcomes of drugs used for smoking cessation were found similar in subjects carrying wild-type and variant alleles of human nicotinic acetylcholine receptor α subunits. Conclusion: In this study, smoking cessation treatment with varenicline was significantly more effective than treatments with nicotine replacement or bupropion in a cohort of Turkish subjects. Smoker/non-smoker status and the clinical outcomes of treatment with pharmacological agents were similar in subjects with wild-type or variant alleles for human nicotinic acetylcholine receptor subunits α3 (CHRNA3), α4 (CHRNA4) and α5 (CHRNA5).

Effects of Genetic Polymorphisms of Drug Transporter ABCB1 (MDR1) and Cytochrome P450 Enzymes CYP2A6, CYP2B6 on Nicotine Addiction and Smoking Cessation.

OBJECTIVES: To determine the effects of genetic polymorphisms of ABCB1 (MDR1), CYP2A6, CYP2B6 on smoking status, and clinical outcomes of smoking cessation therapies in a Turkish population. METHODS: 130 smokers and 130 non-smokers were recruited. Individuals who never smoked were described as non-smokers. 130 smokers were treated with nicotine replacement therapy (NRT) (n = 40), bupropion (n = 47), bupropion + NRT (n = 15), and varenicline (n = 28). Smokers were checked by phone after 12 weeks of treatment whether they were able to quit smoking or not. Genotyping and phenotyping were performed. RESULTS: Cessation rates were as follows; 20.0% for NRT, 29.8% for bupropion, 40.0% for bupropion + NRT, 57.1% for varenicline (p = 0.013). The frequency of ABCB1 1236TT-2677TT-3435TT haplotype was significantly higher in non-smokers as compared to smokers (21.5% vs. 10.8, respectively; p = 0.018). Neither smoking status nor smoking cessation rates were associated with genetic variants of CYP2A6 (p = 0.652, p = 0.328, respectively), or variants of CYP2B6 (p = 0.514, p = 0.779, respectively). CONCLUSION: Genetic variants of the drug transporter ABCB1 and the 1236TT-2677TT-3435TT haplotype was significantly associated with non-smoking status. Neither ABCB1 nor CYP2A6, CYP2B6 genetic variants were associated with smoking cessation rates at the 12th week of drug treatment.

Evaluation of the stability and stratification of propofol and ketamine mixtures for pediatric anesthesia.

BACKGROUND: The combination of propofol and ketamine is commonly used for total intravenous anesthesia. These drugs can be delivered in different syringes or in the same syringe. We hypothesized that the drugs might separate and different concentrations of each drug could be found in different parts of the syringe during the procedure period when they were mixed in 1 syringe. METHODS: Twelve 60-mL polypropylene syringes were prepared by mixing propofol and ketamine as 4 groups on the basis of propofol/ketamine mixture ratios (5:1 and 6.7:1) and propofol solution concentrations. Syringes were placed upright in the vertical position into a rack and kept at room temperature (21.5-22.5°C), in daylight conditions and were not moved for 360 minutes. Samples of the mixture were taken from both the top and the bottom of the syringe. The first 1 mL of the samples was discarded, the following second 1 mL of the samples was filtered using 0.2-µm polytetrafluoroethylene filters and measured twice (n = 6). Samples were taken at the following time intervals: T0, T10, T30, T60, T90, T120, T180, T240, T300, and T360 min. Syringes were checked visually for any color change and separation lines between the drugs. RESULTS: There were no significant differences between the propofol and ketamine concentrations of the top and bottom samples in all 4 groups. In addition, there were no statistically significant changes of propofol and ketamine concentrations of samples over 360 minutes in any of the 4 groups. No visual changes were observed during 6 hours' observation. CONCLUSION: The results of our measurements demonstrated that mixtures of propofol (1% and 2%) and ketamine at 5:1 and 6.7:1 ratios could be used in terms of mixture homogeneity and stability in a polypropylene syringe during a 6-hour period at room temperature.

Relation of the Allelic Variants of Multidrug Resistance Gene to Agranulocytosis Associated With Clozapine.

Clozapine use is associated with leukopenia and more rarely agranulocytosis, which may be lethal. The drug and its metabolites are proposed to interact with the multidrug resistance transporter (ABCB1/MDR1) gene product, P-glycoprotein (P-gp). Among various P-glycoprotein genetic polymorphisms, nucleotide changes in exons 26 (C3435T), 21 (G2677T), and 12 (C1236T) have been implicated for changes in pharmacokinetics and pharmacodynamics of many substrate drugs. In this study, we aimed to investigate the association between these specific ABCB1 polymorphisms and clozapine-associated agranulocytosis (CAA). Ten patients with a history of CAA and 91 control patients without a history of CAA, despite 10 years of continuous clozapine use, were included. Patient recruitment and blood sample collection were conducted at the Hacettepe University Faculty of Medicine, Department of Psychiatry, in collaboration with the members of the Schizophrenia and Other Psychotic Disorders Section of the Psychiatric Association of Turkey, working in various psychiatry clinics. After DNA extraction from peripheral blood lymphocytes, genotyping was performed using polymerase chain reaction and endonuclease digestion. Patients with CAA had shorter duration of clozapine use but did not show any significant difference in other clinical, sociodemographic characteristics and in genotypic or allelic distributions of ABCB1 variants and haplotypes compared with control patients. Among the 10 patients with CAA, none carried the ABCB1 all-variant haplotype (TT-TT-TT), whereas the frequency of this haplotype was approximately 12% among the controls. Larger sample size studies and thorough genetic analyses may reveal both genetic risk and protective factors for this serious adverse event.

The effects of acute tension increase on rat esophageal muscle contractions: An in vitro study.

In long-gap esophageal atresia surgeries, anastomoses can be tensioned by several traction methods in order to establish esophageal continuity. It is unclear whether the etiology of esophageal dysmotility after traction is related with esophageal atresia itself or tensioned esophagus. Therefore, we evaluated the effects of acute in vitro esophageal tension application on esophageal muscle contractility in rats. 26 Wistar rats weighing 250-300 g were included to the study. After diethyl ether anesthesia, proximal segment (PS) and distal segment (DS) of esophagus were removed and suspended in an isolated organ bath kept at 37°C, Krebs-Henseleit solution. Rats were enrolled into four groups including control group (CG, n=14) without tension, 5 g (5G, n=4), 15 g (15G, n=4) and 25 g (25G, n=4) tension groups. In all groups, contractile responses to electrical field stimulation (EFS), carbachol and KCl, and relaxation responses to serotonin were obtained. In CG, higher contractile responses were obtained in PS than DS after EFS. Both PS and DS showed higher contractile amplitudes in 5G with respect to that of CG, 15G and 25G (p<0.05). In 5G, contractile responses to carbachol were significantly increased in both PS and DS with respect to CG (p<0.05). However, contractile amplitudes in response to carbachol were decreased in PS when tension was increased to 15 g and 25 g. In DS, contractile responses in 15G and 25G were lower than 5G, and still higher than CG. Serotonin relaxation responses in PS were decreased when compared to CG at tension levels of 5 g, 15 g and 25 g (p<0.05). In DS, responses to serotonin were also decreased in tension groups. PS had higher contraction amplitudes than DS when contractile responses were obtained by high K(+) (p<0.05). Tension groups of both PS and DS showed increased contractions to high K(+) compared to CG (p<0.05). Increased esophageal tension led to increase in cholinergic responses of smooth muscles as well as in EFS-induced skeletal muscle responses. On the other hand, relaxation responses induced by serotonin decreased. These data indicate that esophageal tension increase impairs esophageal motility in both segments.